What is Beyfortus (nirsevimab) and how is it used for RSV prophylaxis in infants up to 12 months?

What is Beyfortus (Nirsevimab)?

Beyfortus (nirsevimab) is a long-acting monoclonal antibody that provides season-long protection against respiratory syncytial virus (RSV) lower respiratory tract disease with a single intramuscular injection, replacing palivizumab as the first-line prophylactic agent for infants. 1

Mechanism of Action

• Nirsevimab is an RSV F protein-directed fusion inhibitor that prevents the virus from fusing to cellular membranes, thereby neutralizing RSV in the body. 1, 2
• It is a human immunoglobulin G1 (IgG1) monoclonal antibody with an extended half-life that provides protection for approximately 5 months (an entire RSV season). 1, 3

FDA-Approved Indications

• All neonates and infants born during or entering their first RSV season (regardless of gestational age or underlying medical conditions). 1
• Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. 1

Dosing and Administration

First RSV Season (Infants <8 months)

• 50 mg (0.5 mL) for infants weighing <5 kg, administered as a single intramuscular injection. 1, 4
• 100 mg (1 mL) for infants weighing ≥5 kg, administered as a single intramuscular injection. 1, 4

Second RSV Season (High-Risk Children 8-19 months)

• 200 mg total dose administered as two separate 100 mg intramuscular injections at different anatomical sites. 4, 5
• High-risk populations include children with chronic lung disease of prematurity requiring medical support, severe immunocompromise, cystic fibrosis with severe lung disease or poor growth, hemodynamically significant congenital heart disease, and American Indian or Alaska Native children. 4, 5

Timing of Administration

• Administer shortly before or at the onset of the RSV season (typically October through March in most of the continental United States). 6, 4
• Infants born during the RSV season should receive nirsevimab within 1 week of birth, either during the birth hospitalization or in the outpatient setting. 6
• Only a single dose is recommended per RSV season—do not administer additional doses even if breakthrough RSV infection occurs. 6
• Use chronologic age (not corrected age) for preterm infants when determining timing and eligibility. 6

Clinical Efficacy

• Reduces medically attended RSV-associated lower respiratory tract infections by 79% (95% CI 68.5-86.1%). 5, 7
• Reduces RSV-related hospitalizations by 77-83% across clinical trials. 5, 8, 7
• Reduces ICU admissions for RSV by 80% (95% CI 70-86%) and acute respiratory failure by 83% (95% CI 74-90%). 9
• Real-world effectiveness data from Spain, Luxembourg, France, and the USA report 82-90% effectiveness in preventing RSV-associated hospitalizations. 8

Safety Profile

• Adverse events are rare (approximately 1.2% of recipients) and generally mild to moderate in severity. 5, 1
• Rash occurs in 0.9% of recipients versus 0.6% with placebo. 5, 1
• Injection site reactions occur in 0.3% of recipients versus 0% with placebo. 5, 1
• No cases of anaphylaxis or immune-complex disease have been reported in clinical trials. 5

Contraindications

• History of serious hypersensitivity reactions (including anaphylaxis) to nirsevimab or any excipient. 1, 4
• If signs of anaphylaxis or clinically significant hypersensitivity occur, initiate appropriate treatment immediately. 1

Key Advantages Over Palivizumab

• Single dose per season versus five monthly injections required for palivizumab. 4, 5
• Universal recommendation for all infants <8 months versus palivizumab's restriction to approximately 5% of high-risk infants. 5
• Do not administer both agents to the same infant—nirsevimab supersedes palivizumab as the preferred prophylactic. 5

Coadministration with Vaccines

• Nirsevimab can be administered simultaneously with routine childhood vaccines without interfering with immune response. 6
• The rate of adverse events with coadministration is similar to vaccines alone. 6

Important Clinical Considerations

• Nirsevimab is not indicated for prevention of hospital-acquired RSV infection—no evidence supports this use. 6
• Infants with prolonged birth hospitalizations should receive nirsevimab shortly before or promptly after hospital discharge. 6
• Providers in Alaska, Hawaii, Puerto Rico, Guam, U.S. Virgin Islands, and southern Florida should consult local guidance due to variable RSV seasonality. 6
• Do not use both maternal RSVpreF vaccine and infant nirsevimab for most infants—choose one strategy. 5